L0301P13 - Role of the Liver in Metabolism and Detoxification Part 2
Amino Acid Metabolism in the Liver *the liver produces many proteins, both for itself and for release into the blood stream *amino acids are used for: **synthesis of proteins to be released into blood for use in peripheral tissues **synthesis of liver and blood plasma proteins **synthesis of nucleotides and hormones **synthesis of non-essential amino acids **energy production by oxidation **gluconeogenesis Amino Acid Catabolism *occurs in the liver when amino acids are found in excess in the body as they cannot be stored #removal and excretion of the amino group #*liver is the only tissue that can deal with the ammonia produced by amino acid catabolism #*transamination and deanimation #oxidation of the carbon skeleton Transamination *catalysed by transaminases (aminotransferases) *requires cofactor - pyridoxal phosphate (PLP - a cofactor from B group vitamin) *involves the transfer of amino groups from one amino acid to form another *effect of transaminase reactions is to collect the amino groups from many different amino acids into the form of L-glutamate *transaminase enzymes can act as clinical markers of cell damage **will be released from the cell membrane that has been damaged Process #α-ketoglutarate¹ collects amino groups from various amino acids to form L-glutamate and another α-keto acid #L-glutamate becomes an amino group donor #*either contributing to biomolecules formation or feeding nitrogenous waste off into excretion pathways ¹an intermediates of the citric acid cycle Deanimation *enzyme: glutamate dehydrogenase *glutamate releases ammonia into the liver *occurs in the liver and a little in the kidneys Process #glutamate is converted to 2-oxoglutarate (α-keto acid) by glutamate dehydrogenase by cleaving the amino group off #ammonia is produced as a waste product ---- Other Sources of Amino Groups Alanine *from muscle transported through the blood *converts α-ketogluterate to glutamate *pyruvate also produced Glutamine *from muscle and other other issues *two amino groups = loses one to become glutamate Glucose-Alanine-Glutamine Cycle *proteins broken down in muscle releasing amino acids *ammonium ion needs to be transported to the liver thus one transamination reaction occurs forming alanine from pyruvate *alanine and/or glutamine transport NH3 from muscles to liver Glucogenic vs Ketogenic Amino Acids *glucogenic **amino acids can be used to synthesis glucose in the liver *ketogenic **amino acids can be used to synthesise ketones in the liver Fate of Ammonia *ammonia **toxic product from deanimation **must be converted into a soluble, non-toxic chemical for excretion in urine ***urea ****H2N - CO -HN2 ****produced in the liver by the endergonic urea cycle Urea Cycle *is a energy-requiring reaction *occurs in the cytoplasm and mitochondria of liver cells *nitrogen atoms are sourced from 2 places: **ammonia from glutamate enters as carboxyl phosphate **amino acid aspartate *forms fumarate which can be converted into oxaloacetate and feed into the CAC **conversion yields 1 NADH = 2.5 ATP **interconnection of pathways reduce the energetic cost of the urea cycle *urea is highly soluble in water and inert thus it diffuses into the blood and is transported to the kidneys for excretion Excess Ammonia *may be due to **malfunctioning/damage of the liver cell **deficiency of particular enzymes *symptoms: **absorbed by the brain - similar to excess alcohol = strange behaviour *treatment: **low protein diet Drugs and Toxic Compound Metabolism *the liver is major site of metabolism of them *converted from fat soluble to water soluble substances and excreted in urine or bile *two phases: **Phase I - modification ***add oxygen or an electron ***compound becomes more hydrophilic  (more soluble in water and easier to excrete) but also more reactive **Phase II - conjugation ***addition of a group to render the molecule more soluble and able to be excreted in urine *sometimes drugs must be metabolised so that they are activated Xenobiotics *molecules that are toxic to our cells *generally taken up from environmental pollutants or from food